[2,3]-Wittig Rearrangement

The [2,3]-Wittig Rearrangement allows the synthesis of
homoallylic
alcohols by the base-induced rearrangement of allyl ethers at low
temperatures.

Mechanism of the [2,3]-Wittig Rearrangement

The [2,3]-Wittig Rearrangement is a [2,3]-sigmatropic reaction, a thermal
isomerization that proceeds through a six-electron, five-membered cyclic
transition state. A general scheme for [2,3]-sigmatropic reactions is given here:

[2,3]-Sigmatropic reactions encompass a vast number of synthetically useful
variants in terms of both the atom pair involved (X, Y) and the electronic state
(Y: anions, non-bonding electron pairs, ylides).

The transformation of deprotonated allyl ethers into homoallylic alcohols is
the [2,3]-sigmatropic version of the
[1,2]-Wittig Rearrangement, and is therefore termed [2,3]-Wittig
Rearrangement:

These [2,3]-rearrangements feature regioselective carbon-carbon bond
formation with allylic transposition of the oxygen, generation of specific
olefin geometries and transfer of chirality. A discussion of the mechanism,
scope and limitations, stereochemical control and synthetic applications can be
found in the review by Nakai and Mikami (Chem. Rev., 1986,
86, 885-902).

The concerted [2,3]-shift competes with the [1,2]-shift in many cases:

The product ratio varies as a function of the temperature and structural
environment (see also [1,2]-Wittig
Rearrangement). The [2,3]-Wittig Rearrangement should be conducted at a low
temperature to avoid contamination by the [1,2]-product.

The reaction rate depends on the energy gap between HOMO (anion) and LUMO (allyl).
Roughly speaking, the less stable the carbanion, the faster the rearrangement.

For the Thio-[2,3]-Wittig Rearrangement, Nakai reported the following
relative reaction rates: R = Ph > CO2Li > CN > CO2Et >
COMe, and for R' = Ph > H > CH3. Reactions in this series were
conducted at temperatures of from -80 °C to +60 °C.

The scope of the [2,3]-Wittig Rearrangement is mainly defined by the
availability of methods for generating carbanions at temperatures low enough to
minimize the occurrence of the [1,2]-rearrangement. Tin-lithium exchange, for
example, allows the selective preparation of extremely unstable carbanions in a
reaction known as the [2,3]-Wittig-Still rearrangement:

[2,3]-Wittig Rearrangements of propargyl ethers can afford allenic alcohols,
but the scope is relatively limited and the process is not general.

Terminal alkynyl groups, for example, are deprotonated; the use of a second
equivalent of base allows the generation of 1,2-rearrangement products via
dianion intermediates.

Many diastereoselective rearrangements have been reported and chirality
transfer with the generation of new stereocenters can be explained by models for
the transition state based on an envelope conformation. The two putative
pathways are shown below:

A strong preference for E products has been confirmed by numerous
experiments.

An originally chiral carbon becomes a planar sp2 center in the
course of the rearrangement of some asymmetric substrates, while simultaneously
new chiral centers are generated at an originally sp2 center and the
anionic carbon:

Properly designed strategies based on the [2,3]-Wittig Rearrangement are
powerful tools for asymmetric synthesis as exemplified by the many examples
presented in the review by Nakai and Mikami (Chem. Rev., 1986,
86, 885-902).